Audrey M. Bernstein
- ASSISTANT PROFESSOR Ophthalmology
- ASSISTANT PROFESSOR Pharmacology and Systems Therapeutics
B.S., Lehigh University
Ph.D., University of Kentucky Medical Center
Mount Sinai School of Medicine
- Dr. Bernstein is an Assistant Professor at Mount Sinai School of Medicine in the Department of Ophthalmology. She is a full-time researcher working on promoting regenerative healing and preventing fibrotic healing after wounding in the cornea and other tissues.
Special Scholars Award
Research to Prevent Blindness
Corneal Wound Healing
Our lab is studying the mechanisms that regulate wound healing in the cornea. The cornea refracts light as it enters the eye so that a properly focused image reaches the retina. Maintaining corneal transparency is critical for clear, unobstructed vision. When a cornea is wounded by surgery or injury, the wound heals unpredictably, either regeneratively (without scarring) or fibrotically (with scarring). Corneal scars may be opaque, and cause severe visual defects. Our goal is to understand the mechanisms that promote regenerative wound healing over fibrotic healing.
Corneal wound healing begins when cells (fibroblasts) migrate into the wound site. Upon reaching the wound, fibroblasts begin producing repair matrix and differentiate into contractile cells (myofibroblasts) that adhere to the surrounding matrix and pull the matrix fibers together, closing the wound. Proper spacing and alignment of fibers is essential for an optically clear tissue. In a regeneratively healed wound, myofibroblasts disappear by apoptosis, whereas the persistence of myofibroblasts results in the overproduction of extracellular matrix and excessive contraction, leading to scarring. Regulation of both fibroblast migration and myofibroblast differentiation are critical for promoting regenerative repair.
To better understand the molecular basis for cell migration and cell differentiation, we have focused on the role of the urokinase (uPA) pathway during wound healing. uPA is an extracellular serine protease that stimulates both a protease cascade at the cell-matrix interface and an intracellular signaling cascade resulting in cytoskeletal reorganization and cell migration. We have found dramatic differences in the uPA pathway between fibroblasts and myofibroblasts leading us to conclude that this pathway is important for both fibroblast migration and regulation of myofibroblast differentiation.
Future work will examine the importance of the extracellular matrix composition after wounding. The matrix appears to change throughout wound healing and understanding the specific, time-dependent changes is critical to fully understand the interactions of cells and matrix and their specific roles in regulating cell migration and differentiation. Furthermore, this is a particularly exciting time in this field as we recognized that multiple pathways are involved in this very important repair process. Consequently, we are beginning to study uPA pathway interactions with growth factors and their downstream targets in order to develop a comprehensive picture of how corneal healing may be controlled to provide a perfect optical surface to maintain clear vision.
- Cell adhesion and extracellular matrix
- Cell migration
- Cell differentiation
Wang L, Pedroja B, Meyers E, Garcia A, Twining S, Bernstein A. Degradation of internalized αvβ5 integrin is controlled by uPAR bound uPA: Effect on β1 integrin activity and α-SMA stress fiber assembly. PLoS ONE 2012; 7(3).
Wang L, Ko CY, Meyers EE, Pedroja BS, Pelaez N, Bernstein AM. Concentration-dependent effects of transforming growth factor β1 on corneal wound healing. Molecular vision 2011; 17: 2835-2846.
Pedroja BS, Kang LE, Imas AO, Carmeliet P, Bernstein AM. Plasminogen Activator Inhibitor-1 Regulates Integrin αvβ3 Expression and Autocrine TGFβ Signaling. Journal of Biological Chemistry 2009; 284(31): 20708-20717.
Bernstein A, Twining SS, Warejcka DJ, Tall DJ, Masur SK. Urokinase receptor cleavage: a crucial step in fibroblast to myofibroblast differentiation. Molecular Biology of the Cell 2007 Sep; 18(7): 2716-2727.
Greenberg RS, Bernstein AM, Benezra M, Gelman IH, Taliana L, Masur SK. FAK-dependent regulation of myofibroblast differentiation. FASEB 2006; 20 (7): 1006-8.
Warejcka DJ, Vaughan KA, Bernstein AM, Twining SS. Differential conversion of Plasminogen to Angiostatin by Human Corneal Cell Populations. Molecular Vision 2005; 11: 859-868.
Taliana L, Benezra M, Greenberg RS, Masur SK, Bernstein AM. ZO-1: Lamellipodial Localization in a Corneal Fibroblast Wound Model. Invest Ophthalmol Vis Sci 2005; 46: 96-103.
Bernstein AM, Greenberg RS, Taliana LD, Masur SK. Urokinase Anchors uPAR to the Actin Cytoskeleton. Investigative Ophthalmology and Visual Science 2004; 45(9): 2967-2977.
Turner HC, Alvarez LJ, Candia OA, Bernstein AM. Characterization of Serotonergic Receptors in Rabbit, Porcine and Human Conjunctivae. Current Eye Research 2003; 27(4): 205-215.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Bernstein did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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